The use and manufacture of enteric dosage forms are known in the art. Such dosage forms are described in Remington's Pharmaceutical Sciences, 18th ed., Mack Publishing Co., Easton, Pa. (1990). Enteric dosage forms are useful for protecting the contents of the dosage form from the gastric conditions of the stomach and/or to protect gastric tissue from an irritant material contained in the dosage form. A further use for enteric dosages is prevention of a lasting, unacceptable mouth odor resulting from ingestion of substances like garlic or fish oil. Enteric dosage forms are also used to provide slow, controlled, or delayed release of a substance.
Enteric-coated dosage forms are typically produced by a film coating process, where a thin film layer of an acid-insoluble (enteric) polymer is applied to the surface of a pre-manufactured dosage form, such as a tablet, and to a lesser extent hard and soft capsules. The enteric coating method involves spraying an aqueous or organic solution or suspension of one or more enteric polymers onto tumbling or moving tablets or capsules, followed by drying at elevated temperatures.
Enteric soft capsules are described in U.S. Pat. No. 8,685,445, where an acid-insoluble polymer is combined with a water soluble film forming polymer in the presence of an alkaline aqueous solvent. This formulation resulted in acid resistant capsule shells where the enteric polymer was integrated into the capsule shell. This approach eliminated problems associated with enteric coatings, such as the presence of “orange peel” surface formation, also known as surface roughness, mottling, or lack of surface homogeneity. In addition, the integrated acid-insoluble polymers prevented enteric coat integrity failures, such as in the cases of cracking or flaking of the coating.
However, these enteric polymer formulations can result in gel masses prior to capsulation that are often brittle and viscous, which can reduce the efficiency of the overall manufacturing process (e.g., through the formation of twin capsules). These aspects necessitate the use of additional plasticizers or other softening agents. Furthermore, these integrated enteric polymers required the use of volatile alkaline agents, which require additional safety measures to be in place during manufacturing.
Described herein are gastric resistant capsule shells with integrated enteric polymers, which can encapsulate liquid, semi-solid, or solid matrix fills that contains a gastric resistant polymer or polymers at relatively low concentrations, which obviate the aforementioned limitations. In addition, these enteric soft capsules present unexpectedly enhanced enteric properties and require the use of less plasticizing agents. The gel mass is simpler and safer to manufacture because the use of volatile alkali agents is not required. Furthermore, the enteric soft capsules described herein have an increased compatibility with alkali-labile active drug substances.